During the present project period the specific aim of the research to be carried out is to study the mechanism and significance of the stimulation by a variety of external stimulating agents of the metabolism of phosphatidylinositol and related phospholipids, the so-called phospholipid effect. Although other tissues will also be used in this investigation the pineal gland of the rat offers a particularly suitable system for the study of the action of drugs on lipid metabolism, since the gland can be used relatively intact and is innervated only by adrenergic fibers. It is hoped to gain insight into how pharmacological agents such as neurotransmitters, adrenergic receptor blocking drugs, local anesthetics and tranquilizers exert their effects on nervous tissue, and thus to contribute to the clarification of the participation of phosphoinositides in membrane-related phenomena and their interrelationship with other constituents of membranes. The identification of the cell surface receptors involved in the phospholipid effect and of the enzymatic reaction initially affected will receive special attention. The aims of these studies include further the elucidation of the role of inositol, especially in influencing and controlling metabolic processes and lipid interconversions in tissues under study. The possible existence of inositol compartments which are not equally available for participation in phosphatidylinositol formation will also be explored. BIBLIOGRAPHIC REFERENCES: Hauser, G. and Eichberg, J. Identification of cytidine diphosphatediglyceride in the pineal gland of the rat and its accumulation in the presence of DL-propranolol. J. Biol. Chem. 250, 105-112 (1975). Eichberg, J., Shein, H.M. and Hauser, G. Phospholipid metabolism in cultured neuroblastoma and glioma cells incubated with carbamylcholine and norepinephrine. J. Neurochem. 24, 67-70 (1975).